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Pathways of Microcirculatory Endothelial Dysfunction in Obstructive Sleep Apnea: A Comprehensive Ex Vivo Evaluation in Human Tissue.

Authors :
Gavrilin MA
Porter K
Samouilov A
Khayat RN
Source :
American journal of hypertension [Am J Hypertens] 2022 Apr 02; Vol. 35 (4), pp. 347-355.
Publication Year :
2022

Abstract

Background: The mechanism and markers of cardiovascular disease (CVD) in obstructive sleep apnea (OSA) remain unknown. The microcirculation is the site of early changes in OSA patients who are free of CVD risk.<br />Methods: Patients with newly diagnosed moderate to severe OSA (n = 7) were studied before and 12 weeks after intensive treatment with continuous positive airway pressure (CPAP), along with weight and age matched controls (n = 7). Microcirculatory vessels were isolated from gluteal biopsies and changes in critical functional genes were measured.<br />Results: The following genes changed after 12 weeks of intensive CPAP therapy in the microcirculatory vessels: angiotensin receptor type 1 (AGTR-1) (11.6 (3.4) to 6 (0.8); P = 0.019); NADPH oxidase (NOX4) (0.85 (0.02) to 0.79 (0.11); P = 0.016); and dimethylarginine dimethylaminohydrolase (DDAH 1) (1 (0.31) to 0.55 (0.1); P = 0.028). Despite decreased nitric oxide (NO) availability as measured indirectly through brachial artery flow-mediated dilation, endothelial NO synthase (NOS3) did not change with CPAP. Other disease markers of OSA that changed with treatment in the microcirculation were endothelin, hypoxia inducible factor 1a, nuclear factor kappa B, interleukin-8, and interleukin-6.<br />Conclusions: In this ex vivo evaluation of the microcirculation of patients with OSA and no CVD risk, several pathways of CVD were activated supporting that OSA independently induces microcirculatory endothelial dysfunction and serving as disease-specific markers for future pharmacological targeting of OSA-related CVD risk. The findings support the role of renin-angiotensin activation and endothelial oxidative stress in the decreased microcirculatory NO availability in OSA.<br /> (© American Journal of Hypertension, Ltd 2021. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Details

Language :
English
ISSN :
1941-7225
Volume :
35
Issue :
4
Database :
MEDLINE
Journal :
American journal of hypertension
Publication Type :
Academic Journal
Accession number :
34694354
Full Text :
https://doi.org/10.1093/ajh/hpab169